The effect of the oral administration of various antigens on the ocular immune response has been tested in the animal model for severe intraocular inflammatory disease, experimental autoimmune uveoretinitis, which is induced by both retinal S-antigen (S-Ag) and interphotoreceptor retinoid-binding protein (IRBP). Oral tolerance could be induced by repeatedly feeding S-Ag to rats. A putative suppresser cell that was CD8 positive could be isolated from the spleen of such animals and transferred to other animals to induce a similar tolerogenic effect. In addition, the role of the spleen was confirmed in ongoing animal experiments. A pilot study was performed in two patients that showed the induction of such tolerance, and these patients continue to be followed. A randomized masked trial to evaluate the usefulness of S-Ag feeding in patients with intraocular inflammatory diseases finished recruitment in August 1995. An initial evaluation of the data suggests that the S-antigen group may have positively benefited from this therapy.